Prostate Cancer

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oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

Most prostate cancers are adenocarcinomas arising in the peripheral zone of the prostate gland. Most prostate cancers are slow-growing but some prostate cancers are aggressive. The most common sites for metastases are bone and lymph nodes.

  • Prostate cancer is the most common cancer in men and makes up 26% of all male cancer diagnoses in the UK.[2] 
  • The age-standardised incidence of prostate cancer in the UK in 2010 was 104.5 per 100,000 population.
  • It was estimated that the lifetime risk of being diagnosed with prostate cancer in 2008 was 1 in 9 for men in the UK.
  • In developed countries prostate cancer accounts for 15% of male cancers compared with 4% of male cancers in developing countries.
  • Subclinical prostate cancer is common in men aged over 50 years.[3] 

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Risk factors

  • Increasing age is the most important risk factor for developing prostate cancer.[4] However, around 25% of cases occur in men younger than 65.[2] 
  • There is a higher incidence of and mortality from prostate cancer in men of black African-Caribbean family origin compared with white Caucasian men.[2] 
  • If one first-degree relative has prostate cancer, the risk is at least doubled. About 9% of men with prostate cancer have true hereditary prostate cancer. This is defined as three or more affected relatives, or at least two relatives who have developed early-onset disease (before age 55). Patients with hereditary prostate cancer usually have an onset 6-7 years prior to spontaneous cases, but do not differ in any other ways.[5] 
  • Factors such as food consumption, pattern of sexual behaviour, alcohol consumption, exposure to ultraviolet radiation, chronic inflammation and occupational exposure have all been considered as possible risk factors.[5] 
  • There is some evidence to recommend lifestyle changes (lowered intake of animal fat and increased intake of fruit, cereals, and vegetables) in order to decrease the risk of prostate cancer.[5] 

See also the separate article on Prostate Specific Antigen (PSA).

There is no organised screening programme for prostate cancer in the UK but there is an NHS Prostate Cancer Risk Management Programme.[6]

The American College of Physicians recommends that:[7] 

  • Men between the age of 50 and 69 years should be informed about the limited potential benefits and substantial harms of screening for prostate cancer (eg, overdiagnosis, complications of prostate biopsy and side-effects/complications of over-treatment).
  • Men under the age of 50 years, over the age of 69 years, and those men with a life expectancy of less than 10 to 15 years should not be screened for prostate cancer.

A Cochrane review found that:[8] 

  • Prostate cancer screening did not significantly decrease prostate cancer-specific mortality.
  • Only one study reported a 21% significant reduction of prostate cancer-specific mortality in a pre-specified subgroup of men aged 55 to 69 years.
  • There was no significant reduction in prostate cancer-specific and overall mortality.
  • Harms associated with PSA-based screening and subsequent diagnostic evaluations are frequent, and moderate in severity. Overdiagnosis and over-treatment are common and are associated with treatment-related harms.
  • Any reduction in prostate cancer-specific mortality may take up to 10 years to accrue. Therefore, men who have a life expectancy of less than 10 to 15 years should be informed that screening for prostate cancer is unlikely to be beneficial.
  • No studies have examined the independent role of screening by digital rectal examination (DRE).

Prostate cancer screening with the PSA blood test therefore results in at most a small reduction in prostate cancer mortality and leads to considerable diagnostic and treatment related harms. Most men with prostate cancer detected by PSA testing have tumours that will not cause health problems (overdiagnosed), but almost all undergo early treatment (over-treated).[4] 

See the related separate article on Genitourinary History and Examination (Male).

Lower urinary tract symptoms (LUTS) do not particularly raise suspicion of prostate cancer because LUTS are common in older men and are rarely the presenting symptom of prostate cancer. However, locally advanced prostate cancer may cause obstructive LUTS.[9] 

  • Local disease:
    • Raised PSA on screening.
    • Weak stream, hesitancy, sensation of incomplete emptying, urinary frequency, urgency, urge incontinence. The severity of urinary symptoms can be assessed with the International Prostate Symptom Score (I-PSS).
    • Urinary tract infection.
  • Locally invasive disease:
    • Haematuria, dysuria, incontinence.
    • Haematospermia.
    • Perineal and suprapubic pain.
    • Obstruction of ureters, causing loin pain, anuria, symptoms of acute kidney injury or chronic kidney disease.
    • Impotence.
    • Rectal symptoms - eg, tenesmus.
  • Metastatic disease:
    • Bone pain or sciatica.
    • Paraplegia secondary to spinal cord compression.
    • Lymph node enlargement.
    • Loin pain or anuria due to ureteric obstruction by lymph nodes.
    • Lethargy (anaemia, uraemia).
    • Weight loss, cachexia.

Signs

  • Advanced disease: general malaise, bone pain, anorexia, weight loss, obstructive nephropathy, paralysis due to cord compression.
  • Abdominal palpation may demonstrate a palpable bladder due to outflow obstruction.
  • DRE may reveal a hard, irregular prostate gland. Indications of possible prostate cancer are:
    • Asymmetry of the gland.
    • A nodule within one lobe.
    • Induration of part or all of the prostate.
    • Lack of mobility - adhesion to surrounding tissue.
    • Palpable seminal vesicles.
  • The PSA Test is dealt with in the separate article on Prostate Specific Antigen (PSA)
  • PCA3 urine test: superior to PSA total, and percent-free PSA in detection of prostate cancer. The main current indication of the PCA3 urine test may be to determine whether a man needs a repeat biopsy after an initially negative biopsy outcome. The test is expensive and its cost-effectiveness remains to be shown.[5] 
  • Urinalysis to exclude renal and bladder pathology. Urine sent for microscopy, culture and sensitivities.
  • Renal function tests to help exclude renal disease.
  • Prostate biopsy:
    • To help men decide whether to have a prostate biopsy, their PSA level, DRE findings (including an estimate of prostate size), comorbidities, and risk factors (including increasing age and black African-Caribbean family origin) and any history of a previous negative prostate biopsy should be discussed. Prostate biopsy should not be offered just on the basis of serum PSA level alone.[2] 
    • Men who have had a negative first prostate biopsy still have a risk that prostate cancer is present and the risk is slightly higher if the biopsy showed high-grade prostatic intra-epithelial neoplasia, the biopsy showed atypical small acinar proliferation, and digital rectal examination is abnormal.[2] 
    • Prostate biopsy in patients with suspected prostate cancer is usually carried out by a transrectal needle biopsy. Transrectal ultrasonography (TRUS) and biopsy: in men with a raised concentration of PSA, biopsy will miss 10% to 30% of clinically significant prostate cancers.
    • Transperineal template biopsy may be used for patients with suspected prostate cancer who have had a negative or inconclusive transrectal biopsy. Other proposed indications for transperineal template biopsy include mapping to determine the location and extent of prostate cancer as a guide to focal treatment (eg, ablation), and as part of active surveillance of low-risk localised prostate cancer with the aim of reducing the number of biopsies.[10] 
  • TRUS: the classic picture of a hypoechoic area in the peripheral zone of the prostate will not always be seen. It is not useful to replace systematic with targeted biopsies of suspect areas, but additional biopsies of suspect areas may be useful.[5] 
  • Uroflow measurement, measurement of postmicturition residual urine, cystoscopy and imaging of the upper urinary tract (if suspect upper tract dilatation or bladder outlet obstruction).
  • Multiparametric MRI should be considered for men with a negative TRUS core biopsy to determine whether another biopsy is needed.[2] 
  • Multiparametric MRI (or CT if MRI is contra-indicated) should be considered for men with histologically proven prostate cancer if knowledge of the T or N stage (see below) could affect management.[2] 
  • Isotope bone scans should be offered when hormonal therapy is being deferred through watchful waiting to asymptomatic men who are at high risk of developing bone complications.[2] 

Prostate cancer can be divided into:

  • Non-metastatic: either localised disease confined to the prostate gland or locally advanced disease that has spread outside the capsule of the gland but has not spread to organs, other than the seminal vesicles.
  • Metastatic: spread beyond the prostate to local, regional, or systemic lymph nodes, or to other body organs - eg, bone, liver, or brain.

Tumour, node, metastases (TNM) staging for prostate cancer

  • Primary tumour (T):
    • TX: primary tumour cannot be assessed.
    • T0: no evidence of primary tumour.
    • T1: clinically inapparent tumour neither palpable nor visible by imaging.
    • T1a: tumour incidental histological finding in 5% or less of tissue resected.
    • T1b: tumour incidental histological finding in more than 5% of tissue resected.
    • T1c: tumour identified by needle biopsy (eg, because of elevated PSA).
    • T2: tumour confined within prostate.
    • T2a: tumour involves one lobe.
    • T2b: tumour involves both lobes.
    • T3: tumour extends through the prostatic capsule.
    • T3a: extracapsular extension (unilateral or bilateral).
    • T3b: tumour invades seminal vesicle(s).
    • T4: tumour is fixed or invades adjacent structures other than seminal vesicles: bladder neck, external sphincter, rectum, levator muscles and/or pelvic wall.
  • Regional lymph nodes (N):
    • NX: regional lymph nodes cannot be assessed.
    • N0: no regional lymph node metastasis.
    • N1: metastasis in regional lymph node or nodes.
  • Distant metastasis (M); when more than one site of metastasis is present, the most advanced category (pM1c) is used:
    • MX: distant metastasis cannot be assessed.
    • M0: no distant metastasis.
    • M1: distant metastasis.
    • M1a: non-regional lymph node(s).
    • M1b: bone(s).
    • M1c: other site(s).

Histological grading

  • There are several systems for grading the histology. The most commonly used is the Gleason grading system. It estimates the grade of prostate cancer according to its differentiation. A score of two is the most well differentiated tumour and 10 is the most poorly differentiated. Higher scores are associated with a worse prognosis than lower scores.
    • Grade 1: small, uniform glands with minimal nuclear changes.
    • Grade 2: medium-sized acinii, separated by stromal tissue but more closely arranged.
    • Grade 3: marked variation in glandular size and organisation and infiltration of stromal and neighbouring tissues.
    • Grade 4: marked atypical cytology with extensive infiltration.
    • Grade 5: sheets of undifferentiated cells.
  • Prostate cancers are often heterogeneous and the Gleason score is the sum of the two most prominent grades.
  • The Gleason score has been used as the best prognostic indicator for prostate cancer but other molecular indicators are being evaluated.
    • Gleason score of 4 or less: well differentiated; ten-year risk of local progression 25%.
    • Gleason score 5-7: moderately differentiated; ten-year risk of local progression 50%.
    • Gleason score over 7: poorly differentiated; ten-year risk of local progression 75%.

Several factors have been shown to predict the risk of recurrence after treatment of localised prostate cancer:

  • Low risk: PSA <10 ng/mL and Gleason score 6 or below and clinical stage T1-T2a.
  • Intermediate risk: PSA 10-20 ng/mL, or Gleason score 7, or clinical stage T2b.
  • High risk: PSA >20 ng/mL, or Gleason score 8-10, or clinical stage ≥T2c.
  • Men and their partners should be made aware of the effects of prostate cancer and its treatment, including sexual dysfunction, urinary incontinence and radiation-induced enteropathy.
  • Palliative care services should be offered when needed and not reserved for the time of hospice care or at the end of life.

Referral

The National Institute for Health and Care Excellence (NICE) referral guidelines for suspected cancer state:[11] 

  • Men presenting with symptoms suggesting prostate cancer should have a DRE and PSA test after counselling. Symptoms will be related to the lower urinary tract and may be inflammatory or obstructive. Prostate cancer is also a possibility in male patients with any of the following unexplained symptoms: erectile dysfunction, haematuria, lower back pain, bone pain or weight loss, especially in the elderly.
  • Urinary infection should be excluded before PSA testing, especially in men presenting with lower tract symptoms. The PSA test should be postponed for at least one month after treatment of a proven urinary infection.
  • If a hard, irregular prostate typical of a prostate carcinoma is felt on DRE, then the patient should be referred urgently. The PSA should be measured and the result should accompany the referral.
  • Patients do not need urgent referral if the prostate is simply enlarged and the PSA is in the age-specific reference range.
  • In a man with or without LUTS and in whom the prostate is normal on DRE but the age-specific PSA is raised or rising, an urgent referral should be made. Symptomatic patients with high PSA levels should be referred urgently.
  • If there is doubt about whether to refer an asymptomatic man with a borderline level of PSA, the PSA test should be repeated after an interval of one to three months. If the second test indicates that the PSA level is rising, the patient should be referred urgently.
  • Doctors and patients can use Decision Aids together to help choose the best course of action to take.
  • Compare the options »

Treatment options for non-metastatic disease

Treatment options for clinically localised prostate cancer include watchful waiting or observation, active surveillance, radical prostatectomy, external beam radiation therapy, interstitial radiation implants (brachytherapy), cryoablation, androgen deprivation therapy, high-intensity focused ultrasound (HIFU), and focal therapy.[4] 

The management of early-stage prostate cancer remains controversial, especially for tumours detected with PSA testing.[12] The existing evidence is insufficient to determine the relative beneficial and harmful effects of radical prostatectomy and watchful waiting for men with localised prostate cancer.[13] 

Surgery

  • The surgical treatment of prostate cancer consists of radical prostatectomy, which involves removal of the entire prostate gland between the urethra and bladder, and resection of both seminal vesicles, along with sufficient surrounding tissue to obtain a negative margin. The procedure is often accompanied by bilateral pelvic lymph node dissection.[5]
  • Laparoscopic radical prostatectomy is indicated for localised prostate cancer with no evidence of spread beyond the prostate or distant metastases.[14]

Radiotherapy[5]

  • Radiotherapy is an important and valid alternative to surgery as the sole form of curative therapy.
  • There have been no randomised studies comparing radical prostatectomy with either external-beam radiotherapy or brachytherapy for localised prostate cancer.
  • The consensus is that external irradiation offers the same long-term survival results as surgery and provides a quality of life at least as good as that following surgery.
  • Brachytherapy (transperineal implantation of radioactive seeds into the prostate):
    • A decision to use this technique takes into account several prognostic factors, including Gleason score, PSA level and TNM classification.
    • High-dose rate brachytherapy in combination with external beam radiotherapy, and low-dose rate brachytherapy are recommended as a treatment option for localised prostate cancer.[15][16]

Other treatments

  • Cryotherapy: cryotherapy can be used as a primary treatment for patients with localised or locally advanced prostate cancer.[17] Cryotherapy may also be used to treat locally recurrent carcinoma of the prostate that has been refractory to other treatments, such as radiotherapy or hormone therapy.[18]
  • HIFU may be used to treat carcinoma of the prostate, either as a primary or salvage therapy.[19]

There is evidence that, for locally advanced disease, adding androgen suppression to standard treatments (radiation, prostatectomy) can prolong survival.

Options for primary treatment of prostate cancer[5] 

Stage T1a 

  • Watchful waiting: standard treatment for Gleason score ≤ 6 adenocarcinomas and <10-year life expectancy.
  • Active surveillance In patients with >10-year life expectancy; re-staging with TRUS and biopsy is recommended.
  • Radical prostatectomy: optional in younger patients with a long life expectancy, especially for Gleason score ≥7 adenocarcinomas.
  • Radiotherapy: optional in younger patients with a long life expectancy, in particular in poorly differentiated tumours. There are higher complication risks after transurethral resection of the prostate (TURP), especially with interstitial radiation.

Stage T1b-T2b

  • Active surveillance: treatment option in patients with cT1c-cT2a, PSA <10 ng/mL, biopsy Gleason score ≤6, ≤2 biopsies positive, ≤50% cancer involvement of each biopsy; patients with a life expectancy <10 years; patients with a life expectancy >10 years once they are informed about the lack of survival data beyond 10 years; patients who do not accept treatment-related complications.

Stage T1a-T2c 

  • Radical prostatectomy: optional for patients with pT1a. Standard treatment for patients with a life expectancy >10 years who accept treatment-related complications.
  • Radiotherapy: patients with a life expectancy >10 years who accept treatment-related complications; patients with contra-indications for surgery; unfit patients with 5-10 years of life expectancy and poorly differentiated tumours (combination therapy is recommended).
  • Brachytherapy: low-dose rate brachytherapy can be considered for low-risk patients with a prostate volume ≤50 mL and an I-PSS ≤12.
  • Hormonal: symptomatic patients, who need palliation of symptoms, unfit for curative treatment. Anti-androgens are associated with a poorer outcome compared to ‘active surveillance’ and are not recommended.
  • Combination therapy: for high-risk patients, neoadjuvant hormonal treatment and concomitant hormonal therapy plus radiotherapy result in increased overall survival.

Stage T3-T4 

  • Watchful waiting: option in asymptomatic patients with T3, well-differentiated and moderately differentiated tumours, and a life expectancy <10 years who are unfit for local treatment.
  • Radical prostatectomy: optional for selected patients with T3a, PSA <20 ng/mL, biopsy Gleason score ≤8 and a life expectancy >10 years. Patients have to be informed that radical prostatectomy is associated with an increased risk of positive surgical margins, unfavourable histology and positive lymph nodes and that, therefore, adjuvant or salvage therapy such as radiation therapy or androgen deprivation might be indicated.
  • Radiotherapy: T3 with >5-10 years of life expectancy. A combination with hormonal therapy can be recommended.
  • Hormonal: symptomatic patients, extensive T3-T4, high PSA level (>25-50 ng/mL), PSA-doubling time (DT) <1 year. Patient-driven, unfit patients. Hormone monotherapy is not an option for patients who are fit enough for radiotherapy.
  • Combination therapy: overall survival is improved by concomitant and adjuvant hormonal therapy (3 years) combined with external beam radiation.

Stage N+, M0

  • Watchful waiting: asymptomatic patients. Patient-driven (PSA <20-50 ng/mL), PSA DT >12 months. Requires very close follow-up.
  • Radical prostatectomy: optional for selected patients with a life expectancy of >10 years as part of a multimodal treatment approach.
  • Radiotherapy: optional in selected patients with a life expectancy of >10 years, combination therapy with adjuvant androgen deprivation for 3 years is mandatory.
  • Hormonal: standard adjuvant therapy in more than two positive nodes to radiation therapy or radical prostatectomy as primary local therapy. Hormonal therapy should only be used as monotherapy in patients who are unfit for any type of local therapy.
  • Combination therapy: no standard option.

Stage M+

  • Watchful waiting: may have worse survival/more complications than with immediate hormonal therapy. Requires very close follow-up.
  • Radical prostatectomy and radiotherapy are not standard options. Radiotherapy is a therapeutic option in combination with androgen deprivation for treatment of local cancer-derived symptoms.
  • Hormonal: standard option. Mandatory in symptomatic patients.

NICE guidance[2]

Low-risk localised prostate cancer

  • Active surveillance is an option to men with low-risk localised prostate cancer for whom radical prostatectomy or radical radiotherapy is suitable. NICE recommends the following protocol:
    • At enrolment in active surveillance: multiparametric MRI if not previously performed.
      • Year 1 of active surveillance: measure PSA every 3-4 months, DRE every 6-12 months, prostate re-biopsy at 12 months.
      • Years 2-4 of active surveillance: measure PSA every 3-6 months, DRE every 6-12 months.
      • Year 5 and every year thereafter until active surveillance ends: measure PSA every 6 months, DRE every 12 months.
      • Throughout active surveillance: monitor PSA kinetics (may include PSA doubling time and velocity). 
      • If there is concern about clinical or PSA changes at any time during active surveillance, reassess with multiparametric MRI and/or re-biopsy.
  • Radical treatment:
    • The decision to proceed from an active surveillance regimen to radical treatment should be made in the light of the individual man's personal preferences, comorbidities and life expectancy.
    • Radical treatment should be offered to men with localised prostate cancer who have chosen an active surveillance regimen and who have evidence of disease progression.

Intermediate and high-risk localised prostate cancer

  • Active surveillance should be considered for men with intermediate-risk localised prostate cancer who do not wish to have immediate radical prostatectomy or radical radiotherapy.
  • Active surveillance should not be offered to men with high-risk localised prostate cancer.
  • Radical treatment:
    • Radical prostatectomy or radical radiotherapy should be offered to men with intermediate-risk localised prostate cancer, and to men with high-risk localised prostate cancer when there is a realistic prospect of long-term disease control.
    • Men with intermediate and high-risk localised prostate cancer should be offered a combination of radical radiotherapy and androgen deprivation therapy, rather than radical radiotherapy or androgen deprivation therapy alone.
    • Men with intermediate and high-risk localised prostate cancer should be offered 6 months of androgen deprivation therapy before, during or after radical external beam radiotherapy.
    • Continuing androgen deprivation therapy for up to 3 years should be considered for men with high-risk localised prostate cancer.
    • High-dose rate brachytherapy in combination with external beam radiotherapy should be considered for men with intermediate and high-risk localised prostate cancer. Brachytherapy alone should not be offered to men with high-risk localised prostate cancer.

Locally advanced prostate cancer

  • Pelvic radiotherapy should be considered for locally advanced prostate cancer if there is a higher than 15% risk of pelvic lymph node involvement and if neoadjuvant hormonal therapy and radical radiotherapy are to be provided.
  • Immediate postoperative radiotherapy after radical prostatectomy should not be offered, even to men with margin-positive disease.
  • Adjuvant hormonal therapy in addition to radical prostatectomy should not be offered, even to men with margin-positive disease.

Managing relapse after radical treatment

  • Analyse serial PSA levels after radical treatment, using the same assay technique.
  • Biopsy of the prostatic bed should not be offered to men with prostate cancer who have had a radical prostatectomy. Biopsy of the prostate after radiotherapy should only be offered to men with prostate cancer who are being considered for local salvage therapy in the context of a clinical trial.
  • For men with evidence of biochemical relapse following radical treatment and who are considering radical salvage therapy:
    • Routine MRI scanning prior to salvage radiotherapy should not be offered to men with prostate cancer
    • An isotope bone scan should be offered if symptoms or PSA trends are suggestive of metastases.
    • Biochemical relapse (a rising PSA) alone should not necessarily prompt an immediate change in treatment. Biochemical relapse should trigger an estimate of PSA doubling time, based on a minimum of three measurements over at least a 6-month period.
    • Men with biochemical relapse after radical prostatectomy, with no known metastases, should be offered radical radiotherapy to the prostatic bed.
    • Hormonal therapy should not routinely be offered to men with prostate cancer who have a biochemical relapse unless they have symptomatic local disease progression, any proven metastases, or a PSA doubling time of less than 3 months.

Metastatic prostate cancer

  • Bilateral orchidectomy should be offered to all men with metastatic prostate cancer as an alternative to continuous luteinising hormone-releasing hormone (LHRH) agonist therapy.
  • Combined androgen blockade should not be offered as a first-line treatment for metastatic prostate cancer.
  • For men with metastatic prostate cancer who are willing to accept the adverse impact on overall survival and gynaecomastia in the hope of retaining sexual function, anti-androgen monotherapy with bicalutamide can be used.
  • Androgen deprivation therapy (see below) should be started and bicalutamide stopped for men with metastatic prostate cancer who are taking bicalutamide monotherapy and who do not maintain satisfactory sexual function.

Hormonal therapy
Androgen deprivation treatment refers to treatments that act by reducing the effects of testosterone and other androgens, thus inhibiting the progression of prostate cancer. The main treatments used are LHRH agonists and anti-androgens:[20] 

Surgical castration is still considered the ‘gold standard’ for androgen deprivation therapy. Bilateral orchiectomy (total or subcapsular) is a simple surgical procedure. It is easily performed under local anaesthesia. The main drawback is that it may have a negative psychological effect and it is irreversible and does not allow for intermittent treatment.[5] 

  • LHRH agonists (such as goserelin, leuprorelin, and triptorelin) induce castrate levels of testosterone by binding to their associated receptors in the anterior pituitary. The initial stimulation of the receptors may lead to an initial flare-up of testosterone level, lasting up to 10 days. Castrate levels of testosterone are reached within four weeks.
  • Anti-androgens act mainly by inhibiting signalling through the androgen receptor, which leads to apoptosis and inhibition of prostate cancer growth. There are two classes of anti-androgens: steroidal (cyproterone acetate) and non-steroidal (bicalutamide, nilutamide, and flutamide).
  • Newer drugs: other forms of androgen deprivation treatment include LHRH antagonists, such as degarelix, which binds competitively to pituitary LHRH receptors, rapidly reducing luteinising hormone and testosterone levels without the initial testosterone flare.

Prostate cancer may regrow after androgen deprivation treatment, despite castrate levels of testosterone (castration-resistant prostate cancer). Newer drugs used in this phase include abiraterone (which inhibits enzymes needed for androgen biosynthesis) and enzalutamide (which inhibits androgen receptor transfer to the nucleus).

Abiraterone in combination with prednisone or prednisolone is recommended by NICE as an option for the treatment of castration-resistant metastatic prostate cancer only if the disease has progressed on or after one docetaxel-containing chemotherapy regimen.[21] 

For men who are having intermittent androgen deprivation therapy: measure PSA every 3 months and restart androgen deprivation therapy if PSA is 10 ng/mL or above, or if there is symptomatic progression.

Managing adverse effects of hormone therapy

  • Flare phenomenon:[5] 
    • LHRH agonists have become the ‘standard of care’ in hormonal therapy. The main concern is the ‘flare phenomenon’ in advanced disease.
    • The flare phenomenon is associated with bone pain, acute bladder outlet obstruction, obstructive acute kidney injury, spinal cord compression, and fatal cardiovascular events due to hypercoagulation status.
    • The overall clinical impact of this initial flare is unknown.
    • Patients at risk are usually patients with high-volume, symptomatic, bony disease, which account for only 4-10% of M1 patients.
    • Concomitant therapy with an anti-androgen decreases the incidence of clinical flare, but does not completely suppress the risk.
    • Anti-androgens (eg, cyproterone acetate or flutamide) should be started before the LHRH analogue and should be continued for a 2-week period.
    • Some mini-flares also occur with the long-term use of LHRH agonists. The clinical impact is unknown but a mini-flare may be associated with a negative impact on overall survival
  • Hot flushes: medroxyprogesterone, initially for 10 weeks. Consider cyproterone acetate or megestrol acetate to treat troublesome hot flushes if medroxyprogesterone is not effective or not tolerated.
  • Sexual dysfunction: long-term androgen deprivation will cause a reduction in libido and possible loss of sexual function. Consider referring men who are having long-term androgen deprivation therapy, and their partners, for psychosexual counselling. Offer treatment options for erectile dysfunction.
  • Osteoporosis: do not routinely offer bisphosphonates to prevent osteoporosis in men with prostate cancer having androgen deprivation therapy. Offer bisphosphonates to men who are having androgen deprivation therapy and have osteoporosis. Consider denosumab for men who are having androgen deprivation therapy and have osteoporosis if bisphosphonates are contra-indicated or not tolerated.
  • Gynaecomastia: for men starting long-term bicalutamide monotherapy (longer than 6 months), offer prophylactic radiotherapy to both breast buds within the first month of treatment. If radiotherapy is unsuccessful in preventing gynaecomastia, weekly tamoxifen should be considered.
  • Fatigue: this is a recognised side-effect. Offer men who are starting or having androgen deprivation therapy supervised resistance and aerobic exercise at least twice a week for 12 weeks to reduce fatigue and improve quality of life.

Hormone-relapsed metastatic prostate cancer

  • Docetaxel is recommended, within its licensed indications, as a treatment option for men with hormone-refractory prostate cancer only if their Karnofsky performance-status score (a measure of the ability to perform daily tasks) is 60% or more.[22] 
  • It is recommended that treatment with docetaxel should be stopped at the completion of planned treatment of up to 10 cycles, or if severe adverse events occur, or in the presence of progression of disease as evidenced by clinical or laboratory criteria, or by imaging studies. Repeat cycles of treatment with docetaxel are not recommended if the disease recurs after completion of the planned course of chemotherapy.
  • Offer a corticosteroid such as dexamethasone as third-line hormonal therapy after androgen deprivation therapy and anti-androgen therapy to men with hormone-relapsed prostate cancer.
  • Offer spinal MRI to men with hormone-relapsed prostate cancer shown to have extensive metastases in the spine (eg on a bone scan) if they develop any spinal-related symptoms. Do not routinely offer spinal MRI to all men with hormone-relapsed prostate cancer and known bone metastases.

Bone-targeted therapies

  • Do not offer bisphosphonates to prevent or reduce the complications of bone metastases in men with hormone-relapsed prostate cancer.
  • Bisphosphonates for pain relief may be considered for men with hormone-relapsed prostate cancer when other treatments (including analgesics and palliative radiotherapy) have failed.
  • Strontium-89 should be considered for men with hormone-relapsed prostate cancer and painful bone metastases, especially those men who are unlikely to receive myelosuppressive chemotherapy.

Pelvic-targeted therapies

  • Offer decompression of the upper urinary tract by percutaneous nephrostomy or by insertion of a double J stent to men with obstructive uropathy secondary to hormone-relapsed prostate cancer.
  • The option of no intervention should also be discussed with men with obstructive uropathy secondary to hormone-relapsed prostate cancer.

Palliative care

See the separate articles on Palliative Care, Pain Control in Palliative Care, Helping Patients Face Death and Dying and Looking After People With Cancer.

  • Bisphosphonates should be considered for patients with skeletal masses, to prevent osseous complications.
  • Palliative treatments, such as radionuclides, external beam radiotherapy and adequate use of analgesics, should be considered early on in the management of painful bone metastases.
  • Emergency spinal surgery or decompressive radiotherapy should be considered for patients with neurological symptoms thought to be critical.
  • Urinary tract obstruction, acute kidney injury, chronic kidney disease.
  • Sexual dysfunction: erectile dysfunction, loss of libido.
  • Metastatic spread: bone pain, pathological fractures, spinal cord compression.
  • Complications of hormonal therapy:
    • Hot flushes: synthetic progestogens are recommended as first-line therapy for troublesome hot flushes.
    • Gynaecomastia is a common, troublesome complication of long-term bicalutamide monotherapy: men starting long-term bicalutamide monotherapy (>6 months) should receive prophylactic radiotherapy to both breast buds within the first month of treatment.
  • Survival from prostate cancer is strongly related to the stage of the disease at diagnosis.
  • Prostate cancer mortality is strongly related to age, with the highest mortality rates being in older men. In the UK between 2009 and 2011, an average of 73% of prostate cancer deaths were in men aged 75 years and over, and more than 99% were in the 50s and over.
  • In 2005-2009, 81.4% of adult prostate cancer patients in England survived their cancer for five years or more.

Further reading & references

  1. Prostate cancer statistics; Cancer Research UK
  2. Prostate cancer: diagnosis and treatment; NICE Clinical guideline (Jan 2014)
  3. Prostate cancer; ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2013)
  4. Wilt TJ, Ahmed HU; Prostate cancer screening and the management of clinically localized disease. BMJ. 2013 Jan 29;346:f325. doi: 10.1136/bmj.f325.
  5. Guidelines on Prostate Cancer; European Association of Urologists (2013)
  6. Prostate Cancer Risk Management; NHS Cancer Screening Programmes
  7. Qaseem A, Barry MJ, Denberg TD, et al; Screening for prostate cancer: a guidance statement from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2013 May 21;158(10):761-9. doi: 10.7326/0003-4819-158-10-201305210-00633.
  8. Ilic D, Neuberger MM, Djulbegovic M, et al; Screening for prostate cancer. Cochrane Database Syst Rev. 2013 Jan 31;1:CD004720. doi: 10.1002/14651858.CD004720.pub3.
  9. Prostate cancer; NICE CKS, January 2011 (UK access only)
  10. Transperineal template biopsy of the prostate; NICE Interventional Procedure Guideline (October 2010)
  11. Referral for suspected cancer; NICE Clinical Guideline (2005)
  12. Wilt TJ; The Prostate Cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy with watchful waiting for men with clinically localized prostate cancer. J Natl Cancer Inst Monogr. 2012 Dec;2012(45):184-90. doi: 10.1093/jncimonographs/lgs041.
  13. Hegarty J, Beirne PV, Walsh E, et al; Radical prostatectomy versus watchful waiting for prostate cancer. Cochrane Database Syst Rev. 2010 Nov 10;(11):CD006590. doi: 10.1002/14651858.CD006590.pub2.
  14. Laparoscopic radical prostatectomy; NICE Interventional Procedure Guideline (2006)
  15. High dose rate brachytherapy for prostate cancer; NICE (2006)
  16. Low dose rate brachytherapy for prostate cancer; NICE (2005)
  17. Cryotherapy as a primary treatment for prostate cancer; NICE Technology Appraisal, 2005
  18. Cryotherapy for recurrent prostate cancer; NICE Technology Appraisal, 2005
  19. High-intensity focused ultrasound for prostate cancer; NICE Technology Appraisal, 2005
  20. Thomas BC, Neal DE; Androgen deprivation treatment in prostate cancer. BMJ. 2013 Jan 8;346:e8555. doi: 10.1136/bmj.e8555.
  21. Prostate cancer (metastatic, castration resistant) - abiraterone (following cytoxic therapy); NICE Technology Appraisal Guideline, June 2012
  22. Docetaxel for the treatment of hormone refractory prostate cancer; NICE Technology Appraisal, 2006

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Colin Tidy
Current Version:
Peer Reviewer:
Dr John Cox
Document ID:
2673 (v25)
Last Checked:
11/02/2014
Next Review:
10/02/2019